| Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice. | |
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MedLine Citation:
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PMID: 22234995 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The prevalence of diabetes mellitus type 2 could be significantly reduced by early identification of subjects at risk allowing better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the pre-diabetic stage. This study aims at identifying a) prognostic biomarkers predicting the risk of developing GI later in life and b) diagnostic biomarkers reflecting the degree of already manifest GI. To this end, disease development was followed over time in mice and biomarkers were identified using lipidomics and transcriptomics. Young adult ApoE3Leiden mice were treated 12 weeks a high fat diet to induce GI. Blood was collected before and during disease development. The individual extent of GI was determined with a glucose tolerance test and the area under the curve (AUC) was calculated for each animal. Subject-specific AUC values were correlated to the plasma lipidome (t=0) and the white blood cell (WBC) transcriptome (t=0, 6 and 12 weeks) to identify prognostic and diagnostic biomarkers, respectively. The plasma ratio of specific free fatty acids prior to high fat feeding (C16:1/C16:0, C18:1/C18:0 and C18:2/C22:6) was significantly correlated with the AUC and predictive for future GI. Subsequently, the expression level of specific WBC genes (Acss2, Arfgap1, Tfrc, Cox6b2, Barhl2, Abcb4, Cyp4b1, Sars2, Fgf16 and Tceal8) reflected the individual degree of GI during disease progression. Specific plasma free fatty acids as well as their ratio can be used to predict future GI. The expression levels of specific WBC genes can serve as easy accessible markers to diagnose and monitor already existing GI. |
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Authors:
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Suzan Wopereis; Marijana Radonjic; Carina M Rubingh; Marjan van Erk; Age K Smilde; Wim van Duyvenvoorde; Nicole H P Cnubben; Teake Kooistra; Ben van Ommen; Robert Kleemann |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: Physiological genomics Volume: - ISSN: 1531-2267 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815683 Medline TA: Physiol Genomics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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TNO Innovation for life, Earth, Environmental and Life Sciences. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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